LncRNA AK024094 aggravates the progression of breast cancer through regulating miRNA-181a.

OBJECTIVE: The aim of this study was to investigate the role of long noncoding ribonucleic acids (lncRNAs) AK024094 in regulating the progression of breast cancer (BCa) and the potential mechanism. Our findings might help to provide a theoretical basis for the targeted therapy of BCa. PATIENTS AND METHODS: The relative expression level of lncRNA AK024094 in BCa and adjacent normal tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The prognostic potential of AK024094 in BCa was assessed by the Kaplan-Meier method. Meanwhile, AK024094 level in BCa cell lines was detected by qRT-PCR as well. The regulatory effects of AK024094 on the proliferative, migratory, and invasive abilities of MDA-MB-468 and MCF-7 cells were evaluated by functional assays. The Dual-Luciferase Reporter Gene Assay was applied to verify the binding between AK024094 and miRNA-181a. In addition, the rescue experiments were conducted to uncover the role of AK024094/miRNA-181a in the progression of BCa. RESULTS: AK024094 was significantly upregulated in BCa tissues and cell lines. Compared with BCa patients with low expression of AK024094, the tumor staging of those with a high level of AK024094 was remarkably worse. Meanwhile, the rate of distant metastasis was significantly higher, and the overall survival was shorter in BCa patients with high expression of AK024094. The knockdown of AK024094 significantly attenuated the proliferative, migratory, and invasive abilities of MDA-MB-468 and MCF-7 cells. Subsequently, miRNA-181a was predicted and verified as the target of AK024094. A negative correlation was identified between the expression levels of AK024094 and miRNA-181a in BCa. Furthermore, the knockdown of miRNA-181a partially reversed the effect of AK024094 on cellular behaviors of BCa cells. CONCLUSIONS: AK024094 aggravates the malignant progression of BCa, and is closely related to tumor staging, distant metastasis, and poor prognosis of BCa. In addition, AK024094 accelerates the proliferation and metastasis of BCa cells by targeting miRNA-181a.

A study of the mechanisms involved in relaxation induced by 17-beta-estradiol in the isolated rabbit aorta.

We used the isolated rabbit aorta to examine the mechanisms that mediate the known vasodilatation induced by 17-beta-estradiol. Our results suggest that nitric oxide (NO), the inhibition of Ca2+ release from intracellular stores through the IP3 pathway and Ca2+ influx through potential-dependent calcium channels (PDCs) seem to be involved. Prostaglandins and adrenergic beta receptors do not influx, intracellular Ca2+ release, NO, cyclic guanine monophosphate (cGMP), prostaglandins and adrenergic beta receptors.

Effect of progesterone on the contractile response of isolated pulmonary artery in rabbits.

The purpose of this study was to assess the direct effect of progesterone on rabbit pulmonary arteries and to examine the mechanism of its action. Rings of pulmonary artery from male rabbits were suspended in organ baths containing Krebs solution, and isometric tension was measured. The response to progesterone was investigated in arterial rings contracted with noradrenaline (NA), KCl, and CaCl2. The effects of endothelium, nitric oxide (NO), prostaglandins, cyclic GMP (cGMP), and the adrenergic beta-receptor on progesterone-induced relaxation were also assessed. Progesterone inhibited the vasocontractivity to NA, KCl, and CaCl2, and relaxed rabbit pulmonary artery. The relaxing response of progesterone in pulmonary artery was significantly reduced by removal of endothelium, inhibitors of nitric oxide synthase and guanylate cyclase, but not by prostaglandin synthase inhibitor and blockage of the adrenergic beta-receptor. In Ca2+-free (0.1 mM EGTA) Krebs solution, progesterone inhibited NA-induced contraction that was intracellular Ca2+-dependent, but didn't affect the contraction of extracellular Ca2+-dependent component. Our results suggest that progesterone induces relaxation of isolated rabbit pulmonary arteries partially via NO and cGMP. Progesterone may also inhibit Ca2+ influx through potential-dependent calcium channels (PDCs) and Ca2+ release from intracellular stores.

[Effect of cholecystokinin and secretin on contractile activity of isolated gastric muscle strips in guinea pigs].

Motility of gastric strips taken from different regions of guinea pig stomach were simultaneously recorded in 8 tissue chambers to test the effect of cholecystokinin-octapeptide (CCK-8) and secretin. It was found that CCK-8 could increase (1) all regional circular and longitudinal muscular tension at rest, (2) the frequency of contractions in body, antrum and pylorus, (3) the mean contractile amplitude of antral circular strips, (4) the motility index of pylorus, but decrease the mean contractile amplitude of body and antral longitudinal strips. All the CCK-8 effects could not be blocked by atropine or indomethacin. Secretin was without effect on gastric smooth muscle activity.

[The relationship between changes in concentration of blood sugar and period of interdigestive myoelectric complex].

We studied the relationship between changes in blood sugar level and periods of interdigestive myoelectric complex (IDMEC) in dogs, and found that the blood sugar concentration varied in each phase of IDMEC cycles, being the highest in phase I and the lowest in phase III. After intravenous injection of phentolamine or propranolol, the cyclic fluctuation of blood sugar level was abolished but the duodenal IDMEC still persisted. After vagotomy, blood sugar concentration was higher than that in fasting dogs and still showed fluctuations in the IDMEC cycle.

Dietary retinol: prevention or promotion of carcinogenesis in humans?

A number of epidemiologic studies have found that 'vitamin A' is associated with a reduced risk for human cancers. Dietary vitamin A indices reflect intake of several compounds in the diet including retinol and pro-vitamin A carotenoids such as beta-carotene, and recent cancer epidemiology studies have attempted to distinguish effects of retinol from those of beta-carotene. While beta-carotene has been associated consistently with a reduced risk for a number of human cancers, particularly epithelial cancers, retinol is generally found to be unassociated with, or positively associated with, risk for many cancers. An apparent enhancement of carcinogenesis has been observed in numerous studies, particularly for cancer of the esophagus, oral cavity, pharynx, larynx, stomach, colon, and rectum. While this finding could be artifactual, experimental studies in animals as well as mechanistic considerations suggest that this effect deserves serious consideration. As discussed in this article, an apparent enhancement of carcinogenesis could be related to an ethanol/retinol interaction, and/or a mechanism involving pro-oxidant activity of retinol but anti-oxidant activity of beta-carotene. This article concludes with suggestions for further research to help clarify the association between retinol and human carcinogenesis.

Dentition, oral hygiene, and risk of oral cancer: a case-control study in Beijing, People's Republic of China.

A case-control study of oral cancer was conducted in Beijing, People's Republic of China. The study was hospital-based and controls were hospital in-patients matched to the cases by age and gender. A total of 404 case/control pairs were interviewed. This paper provides data regarding oral conditions as risk factors for oral cancer, with every patient having an intact mouth examined (pre-operation among cases) using a standard examination completed by trained oral physicians. After adjustment for tobacco smoking and alcohol consumption, poor dentition--as reflected by missing teeth--emerged as a strong risk factor for oral cancer: the odds ratio (OR) for those who had lost 15-32 teeth compared to those who had lost none was 5.3 for men and 7.3 for women and the trend was significant (P less than 0.01) in both genders. Those who reported that they did not brush their teeth also had an elevated risk (OR = 6.9 for men, 2.5 for women). Compared to those who had no oral mucosal lesions on examination (OR = 1.0), persons with leukoplakia and lichen planus also showed an elevated risk of oral cancer among men and women. Denture wearing per se did not increase oral cancer risk (OR = 1.0 for men, 1.3 for women) although wearing metal dentures augmented risk (OR = 5.5 for men). These findings indicate that oral hygiene and several oral conditions are risk factors for oral cancer, independently of the known risks associated with smoking and drinking.

Tobacco smoking, alcohol consumption, and risk of oral cancer: a case-control study in Beijing, People's Republic of China.

A case-control study of oral cancer was conducted in Beijing, People's Republic of China (PRC). The study was hospital-based and controls were hospital in-patients matched for age and gender with the cases. The response rates for cases and controls were 100 percent and 404 case/control pairs were interviewed. Tobacco smoking and alcohol consumption emerged as independent risk factors for oral cancer. For tobacco smoking, the association was considerably stronger for smokers of pipes than for smokers of cigarettes. For all kinds of tobacco, expressed as cigarette equivalents, the odds ratio (OR) for total pack-years smoked, among males, rose from 1.0 in never-smokers to 3.7 (95 percent confidence interval, 1.8-7.4) in the highest quintile of exposure. Similar results were found for females. The association with tobacco consumption was strong for squamous cell carcinoma but there was no trend in risk associated with tobacco for adenocarcinomas and other histologic types. So few women reported consuming alcohol that this variable could be examined only in males. Risk in the highest category of total lifetime intake of alcohol relative to that in lifetime abstainers was 2.3 (1.1-4.8) with a significant trend in risk with increasing dose (P less than 0.002). The combined effects of tobacco and alcohol appear to be approximately multiplicative in males. The attributable risk of oral cancer for tobacco among tobacco smokers was estimated as 34 percent (45 percent among males and 21 percent among females); for alcohol consumption in males the estimate was 23 percent.

A second follow-up of mortality in a cohort of pesticide applicators.

A cohort of 16,124 male pesticide applicators was matched with Social Security Administration and National Death Index (NDI) files through December 31, 1984. In all, 1,082 deaths were ascertained, and death certificates were obtained for 994 (92%). The standardized mortality ratio (SMR) for all causes of death was 98. Although a number of specific causes of death showed SMRs significantly below 100, only one category of cause of death showed a significantly elevated SMR--cancer of the lung, with an SMR of 135. Termite control operators (TCO)--the group with the greatest likelihood of exposure to chlordane and heptachlor--had an SMR for lung cancer of 97, compared with 158 for other pesticide operators. The excess of lung cancer in the non-TCO workers was limited to operators employed as such for less than five years.